Fludarabine-Based Conditioning for Marrow Transplantation From Unrelated Donors in Severe Aplastic Anemia: Early Results of a Cyclophosphamide Dose De-Escalation Study Show Life-Threatening Adverse Events at Predefined Cyclophosphamide Dose Levels
Year of Publication
Tolar, J; Deeg, HJ; Arai, S; Horwitz, M; Antin, JH; McCarty, JM; Adams, RH; Ewell, M; Leifer, ES; Gersten, ID; Carter, SL; Horowitz, MM; Nakamura, R; Pulsipher, MA; Difronzo, NL; Confer, DL; Eapen, M; Anderlini, P
Biol Blood Marrow Transplant
Excessive adverse events were encountered in a Phase I/II study of cyclophosphamide (CY) dose deescalation in a fludarabine-based conditioning regimen for bone marrow transplantation from unrelated donors in patients with severe aplastic anemia. All patients received fixed doses of antithymocyte globulin, fludarabine, and low-dose total body irradiation. The starting CY dose was 150 mg/kg, with deescalation to 100 mg/kg, 50 mg/kg, or 0 mg/kg. CY dose level 0 mg/kg was closed due to graft failure in 3 of 3 patients. CY dose level 150 mg/kg was closed due to excessive organ toxicity (n = 6) or viral pneumonia (n = 1), resulting in the death of 7 of 14 patients. CY dose levels 50 and 100 mg/kg remain open. Thus, CY at doses of 150 mg/kg in combination with total body irradiation (2 Gy), fludarabine (120 mg/m(2)), and antithymocyte globulin was associated with excessive organ toxicity.